dbSNP rs6465657: LMTK2:c.998+17C>T (chr7-98187015-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014916.4(LMTK2):c.998+17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 1,596,282 control chromosomes in the GnomAD database, including 196,711 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.37 ( 13406 hom., cov: 33)

Exomes 𝑓: 0.49 ( 183305 hom. )

Consequence

LMTK2
NM_014916.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.617

Variant links:

Genes affected

LMTK2 (HGNC:17880): (lemur tyrosine kinase 2) The protein encoded by this gene belongs to the protein kinase superfamily and the protein tyrosine kinase family. It contains N-terminal transmembrane helices and a long C-terminal cytoplasmic tail with serine/threonine/tyrosine kinase activity. This protein interacts with several other proteins, such as Inhibitor-2 (Inh2), protein phosphatase-1 (PP1C), p35, and myosin VI. It phosporylates other proteins, and is itself also phosporylated when interacting with cyclin-dependent kinase 5 (cdk5)/p35 complex. This protein involves in nerve growth factor (NGF)-TrkA signalling, and also plays a critical role in endosomal membrane trafficking. Mouse studies suggested an essential role of this protein in spermatogenesis. [provided by RefSeq, Oct 2009]

LMTK2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMTK2	NM_014916.4 link	c.998+17C>T		intron_variant	Intron 9 of 13	ENST00000297293.6	NP_055731.2	Q8IWU2
LMTK2	XM_011515981.4 link	c.992+17C>T		intron_variant	Intron 9 of 13		XP_011514283.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMTK2	ENST00000297293.6 link	c.998+17C>T		intron_variant	Intron 9 of 13	1	NM_014916.4	ENSP00000297293.5		Q8IWU2

Frequencies

GnomAD3 genomes

AF:

0.373

AC:

56662

AN:

152012

Hom.:

13407

Cov.:

show subpopulations

Gnomad AFR

AF:

0.111

Gnomad AMI

AF:

0.471

Gnomad AMR

AF:

0.352

Gnomad ASJ

AF:

0.581

Gnomad EAS

AF:

0.138

Gnomad SAS

AF:

0.232

Gnomad FIN

AF:

0.462

Gnomad MID

AF:

0.608

Gnomad NFE

AF:

0.536

Gnomad OTH

AF:

0.430

GnomAD3 exomes

AF:

0.405

AC:

96530

AN:

238114

Hom.:

23378

AF XY:

0.415

AC XY:

53363

AN XY:

128538

show subpopulations

Gnomad AFR exome

AF:

0.101

Gnomad AMR exome

AF:

0.248

Gnomad ASJ exome

AF:

0.593

Gnomad EAS exome

AF:

0.139

Gnomad SAS exome

AF:

0.234

Gnomad FIN exome

AF:

0.472

Gnomad NFE exome

AF:

0.545

Gnomad OTH exome

AF:

0.479

GnomAD4 exome

AF:

0.487

AC:

703442

AN:

1444152

Hom.:

183305

Cov.:

AF XY:

0.483

AC XY:

346528

AN XY:

717764

show subpopulations

Gnomad4 AFR exome

AF:

0.0969

Gnomad4 AMR exome

AF:

0.260

Gnomad4 ASJ exome

AF:

0.587

Gnomad4 EAS exome

AF:

0.120

Gnomad4 SAS exome

AF:

0.237

Gnomad4 FIN exome

AF:

0.479

Gnomad4 NFE exome

AF:

0.537

Gnomad4 OTH exome

AF:

0.473

GnomAD4 genome

AF:

0.372

AC:

56645

AN:

152130

Hom.:

13406

Cov.:

AF XY:

0.363

AC XY:

27013

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.110

Gnomad4 AMR

AF:

0.351

Gnomad4 ASJ

AF:

0.581

Gnomad4 EAS

AF:

0.138

Gnomad4 SAS

AF:

0.232

Gnomad4 FIN

AF:

0.462

Gnomad4 NFE

AF:

0.536

Gnomad4 OTH

AF:

0.427

Alfa

AF:

0.510

Hom.:

48571

Bravo

AF:

0.360

Asia WGS

AF:

0.179

AC:

623

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

6.8

DANN

Benign

0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over